Polyphenol Microbial Metabolites Exhibit Gut and Blood–Brain Barrier Permeability and Protect Murine Microglia against LPS-Induced Inflammation

Abstract

Increasing evidence supports the beneficial effects of polyphenol-rich diets, including the traditional Mediterranean diet, for the management of cardiovascular disease, obesity and neurodegenerative diseases. However, a common concern when discussing the protective effects of polyphenol-rich diets against diseases is whether these compounds are present in systemic circulation in their intact/parent forms in order to exert their beneficial effects in vivo. Here, we explore two common classes of dietary polyphenols, namely isoflavones and lignans, and their gut microbial-derived metabolites for gut and blood–brain barrier predicted permeability, as well as protection against neuroinflammatory stimuli in murine BV-2 microglia. Polyphenol microbial metabolites (PMMs) generally showed greater permeability through artificial gut and blood–brain barriers compared to their parent compounds. The parent polyphenols and their corresponding PMMs were evaluated for protective effects against lipopolysaccharide-induced inflammation in BV-2 microglia. The lignan-derived PMMs, equol and enterolactone, exhibited protective effects against nitric oxide production, as well as against pro-inflammatory cytokines (IL-6 and TNF-α) in BV-2 microglia. Therefore, PMMs may contribute, in large part, to the beneficial effects attributed to polyphenol-rich diets, further supporting the important role of gut microbiota in human health and disease prevention.

Bioactive Polyphenols and Neuromodulation: Molecular Mechanisms in Neurodegeneration

“…Microbial metabolites derived from dietary lignans, a class of polyphenols, like equol and enterolactone, passively cross both the gut and BBB barriers and show protective ability against inflammation in microglia [128]. A recent study demonstrates that microbial polyphenol metabolites could be transported across the BBB endothelium [129].…”

Neuroprotective Effects of Pomegranate Juice against Parkinson’s Disease and Presence of Ellagitannins-Derived Metabolite—Urolithin A—In the Brain

“…Studies on dietary polyphenols suggest their beneficial role against Parkinson's disease (PD), which is mainly attributed to antioxidant, anti-inflammatory, and anti-apoptotic activity [1]. The current research trends also cover their metabolic derivatives, in particular, bioavailable gut microbiota metabolites, which offer a novel preventive approach for the disease [2].…”

Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses

“…All 23 compounds were located in the HIA 99% confidence ellipse, and the absorption grade (Table 1) indicated that all the compounds had good absorption except one, which had moderate absorption. BBB grade predictions indicated that all compounds had medium or very low BBB permeability [24]. Regarding the CYP2D6 inhibition predictions, no compounds inhibited this enzyme and none cause serious drug interaction toxicity.…”